Staphylococcus aureus is an important pathogen that continues to cause a significant number of community-acquired and nosocomial infections worldwide. The sophisticated interplay between host and bacterium is still not completely understood, however, successful colonization is presumed to be the defining event lead to initiation of an infection. MSCRAMM® (Microbial Surface Components Recognizing Adhesive Matrix Molecules) proteins are a family of cell-surface adhesins that recognize and specifically bind to distinct components within host tissues or to serum-conditioned implanted biomaterials such as catheters, artificial joints, and vascular grafts. Once S. aureus have successfully adhered and colonized host tissues, expression of specific genes are altered resulting in phenotype that is more resistant to antimicrobials.
The dramatic increase in methicillin-resistant bacteria coupled with the recent emergence of vancomycin-resistant isolates have accelerated and broadened the interest in developing novel therapeutics against S. aureus. MSCRAMM® proteins provide an excellent target for immunological attack by antibodies. MSCRAMM® protein antibodies exhibit at least two biological properties; initially the highly specific antibodies prevent microbial adherence or recolonization of host tissues or biomaterials and secondly the increased level of MSCRAMM® protein antibodies bound to the cell wall facilitate a rapid clearance of the organism through opsonophagocytosis.
However, it has still remained a problem to identify and utilize the information concerning MSCRAMMs® from S. aureus, such as the fibronectin binding protein, to generate effective monoclonal antibodies because of the variability in the binding properties of the different MSCRAMMs® and their role in infectivity and spread of bacterial infections. Recently, Brennan and Colleagues, Vaccine 17:1846–1857 (1999) demonstrated that the D-2 peptide from FnbpB expressed on the surface of two different plant viruses were highly immunogenic in mice and rats. They later showed that this polyclonal antisera was protective against endocarditis and weight loss associated with S. aureus bacteraemia (Rennermalm et.al. Vaccine 19:3376–3383 (2001)). On the other hand, it has been a problem to develop monoclonal antibodies which can be generated from the fibronectin binding proteins and/or their active fragments and which can be use to inhibit or impair the binding of staphylococcal Fnbp to fibronectin and thus be useful in methods of preventing or treating staphylococcal infections. It has thus remained a highly desirable goal in the field of infectious diseases to develop monoclonal antibodies and other compositions which are successful in treating and preventing a wide variety of staph infections, particularly by inhibiting or impairing the bacteria's ability to bind to fibronectin.